Shire Reports Results from Exploratory Study for Vyvanse(R) as
Adjunctive Therapy in Adults with Significant Cognitive Impairments
with Partially or Fully Remitted Major Depressive Disorder

PHILADELPHIA, December 8,
2011/PRNewswire-FirstCall/ --Shire plc (LSE:
SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical
company, today announced positive Phase II results in a prospective
clinical study of Vyvanse(R) (lisdexamfetamine dimesylate)
Capsules, (CII) as adjunctive therapy to primary antidepressant
treatment in adults with partial or full remission of recurrent
major depressive disorder (MDD) and significant, persistent
cognitive impairments. Lisdexamfetamine dimesylate is a
prescription medicine currently approved in the US, Canada, and
Brazil for the treatment of Attention-Deficit/Hyperactivity
Disorder (ADHD). Vyvanse should only be used to treat
ADHD.

Vyvanse is a stimulant medication and federally
controlled substance (CII) because it can be abused or lead to
dependence. Misuse of stimulants may cause sudden death and serious
cardiovascular adverse events.

Shire is investigating the use of Vyvanse as
adjunctive therapy for patients with MDD. Some patients with MDD
may continue to have cognitive impairment despite resolution of
depressive symptoms following antidepressant therapy, although the
time course and prevalence of cognitive symptoms in patients with
MDD has not been fully characterized. This study, which examined
MDD patients with partially or fully remitted symptoms of
depression, met its primary end point, which was, change from
baseline to end point in the Global Executive Composite (GEC)
T-score of the Behavioral Rating Inventory of Executive Function -
Adult Version (BRIEF-A) self-report. The BRIEF-A (self-report) is a
75-item instrument that assesses behaviors associated with specific
domains of executive functions in adults. This scale is used in a
variety of conditions in addition to depression.

This exploratory, double-blind,
placebo-controlled, parallel-group, multi-center study consisted of
a two-week screening period, a nine-week double-blind period and a
two-week single-blind period. During the entire study, subjects
continued taking established maintenance doses of antidepressant
monotherapy. Subjects in this study had mild or less than mild
depressive symptoms (total score of less than or equal to 18 on the
Montgomery-Asberg Depression Rating Scale [MADRS] at screening and
baseline). The screening was followed by 1:1 randomization to
Vyvanse (n = 71) or placebo (n = 72) augmentation for 9 weeks.
Double-blind Vyvanse (or placebo) was administered orally as
adjunctive therapy (20 to 70 mg per day, titrated over the initial
6 weeks), with the optimal individual dose being continued during a
3-week dose maintenance period. A 2-week single-blind phase
followed the double-blind phase wherein all subjects were
administered placebo.

On the primary efficacy measure, GEC T-score of
the BRIEF-A self-report, Vyvanse was superior to placebo. "These
data are intriguing in that they remind us of the impairment in
executive functioning that patients may continue to manifest with
mild depressive symptoms," stated Dr. Jeffrey Jonas, Senior Vice
President of Research and Development for Shire's Specialty
Pharmaceuticals business. "We will explore with regulatory agencies
how these new findings might support our development program for
Vyvanse as an adjunctive therapy in patients with MDD."

On a secondary end point, mean change in MADRS
total score from baseline to end point, Vyvanse was superior to
placebo. The MADRS is a validated scale which is commonly used by
investigators to assess the severity of depressive illness. "The
results of this secondary end point (MADRS) reinforce Shire's
decision to investigate Vyvanse as adjunctive therapy in MDD. This
trial reflects Shire's approach to patient-centric targeting to
potentially optimize outcomes in otherwise heterogeneous
disorders," added Dr. Jonas.

Over all periods of the study, 24 subjects (out
of 143) discontinued (11 on Vyvanse and 13 on placebo) treatment.
During the double-blind phase, 5 subjects withdrew due to an
adverse event (4 on Vyvanse and 1 on placebo). The 4 events which
led to discontinuation from Vyvanse were loss of consciousness,
suicidal ideation, rash, and worsening of depression. In the
placebo group, 1 subject discontinued due to headaches. During the
double-blind phase, 5 serious adverse events (SAEs) were reported:
2 on Vyvanse (aforementioned loss of consciousness [related],
suicidal ideation [not related]), and 3 on placebo (viral
gastroenteritis, rhabdomyolysis, and salmonellosis).
Treatment-emergent adverse events (TEAEs) (greater than or equal to
5% and at least two times placebo rate) occurring in the Vyvanse
treatment arm were decreased appetite (22.5%), insomnia (14.1%),
urinary tract infection (9.9%), hyperhidrosis (5.6%), and
somnolence (5.6%). Mean changes in blood pressure and pulse were
all consistent with the current product labeling in ADHD. There
were no notable effects on ECG or clinical laboratory
assessments.

About This Study

A total of 143 subjects (aged 18 to 55) entered
the study with at least 8 weeks of maintenance on their
antidepressant monotherapy. Permitted antidepressants included the
generic or branded forms of selective serotonin reuptake inhibitors
(SSRIs). The subjects had no greater than mild depressive symptoms
(MADRS total score less than or equal to 18) and continued to
exhibit significant executive function impairments (EFI; greater
than or equal to1 standard deviation from normal; GEC T-score of
greater than or equal to60 on the BRIEF-A self-report) during the
screening period and at baseline. The subsequent 9-week
double-blind phase consisted of a 6-week dose-optimization period
titrating Vyvanse from the initial 20-mg dose to an optimal dose of
up to 70 mg of Vyvanse or matching placebo, and followed by a
3-week dose maintenance period to evaluate clinical response.
Subjects who completed the double-blind phase of the study entered
a single-blind phase with placebo over a 2-week period to evaluate
the maintenance of treatment response and safety of the withdrawal
of amphetamine. Subjects with either a prior diagnosis of ADHD or
who fulfilled DSM-IV-TR(R) criteria for ADHD were excluded.
Subjects who had symptomatic manifestations that contraindicated
treatment with Vyvanse or may have confounded efficacy or safety
assessments were also excluded. In addition, subjects treated with
medications such as serotonin-norepinephrine reuptake inhibitors
(SNRIs), typical or atypical antipsychotics, mood stabilizers,
tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs)
were excluded from the study.

The primary efficacy was the mean change in GEC
T-scores of the BRIEF-A (self-report) from baseline to the end of
the 9-week double-blind phase. Additionally, the study included a
number of secondary end points. Safety assessments included TEAEs,
vital signs, 12-lead ECG, clinical laboratory assessments, and
Suicidality Tracking Scale (STS).

About Vyvanse(R)

INDICATION

Vyvanse is a prescription medicine for the
treatment of ADHD in children ages 6 to 17 and adults. Vyvanse
should be used as part of a total treatment program that may
include counseling or other therapies.

IMPORTANT SAFETY INFORMATION

Vyvanse is a federally controlled substance (CII)
because it can be abused or lead to dependence. Keep in a safe
place to prevent misuse and abuse. Selling or giving away Vyvanse
may harm others, and is illegal. Vyvanse is a stimulant. Misuse of
stimulants may cause sudden death and serious heart
problems.

- Vyvanse should not be taken by patients who
have:

Heart disease or
hardening of the arteries, moderate to severe high
blood pressure,
overactive thyroid gland (hyperthyroidism), glaucoma,
agitated states, a
history of drug abuse, taken an anti-depression medicine
called a monoamine
oxidase inhibitor (MAOI) within the last 14 days, or
sensitivity to, are
allergic to, or had a reaction to other stimulant medicines.

- Vyvanse is a stimulant medicine. The following
have been reported with use
of stimulant medicines.

Heart-related
problems:

- sudden death in patients who have heart
problems or heart defects
- stroke and heart attack in adults
- increased blood pressure and heart rate

Tell your doctor if you
or your child have any heart problems, heart defects,
high blood pressure, or
a family history of these problems. Call your doctor
right away if you or
your child have any signs of heart problems such as chest
pain, shortness of
breath, or fainting while taking Vyvanse.

Mental (Psychiatric) problems:

All Patients

- new or worse behavior and thought
problems
- new or worse bipolar illness
- new or worse aggressive behavior or
hostility

Children and Teenagers

- new psychotic symptoms (such as hearing
voices, believing things that are
not true, are suspicious) or new
manic symptoms

Tell your doctor about
any mental problems you or your child have, or about
a family history of
suicide, bipolar illness, or depression. Call your
doctor
right away if you or
your child have any new or worsening mental symptoms or
problems while taking
Vyvanse, especially seeing or hearing things that are not
real, believing things
that are not real, or are suspicious.

- Serious side effects have been reported with
use of stimulant medicines
such as Vyvanse, including:
- seizures, mainly
in patients with a history of seizures
- eyesight changes
or blurred vision
- motion and
verbal tics. Patients with tics or Tourette's syndrome may
experience a
worsening of symptoms while taking Vyvanse.
- slowing of
growth. Your child should have his or her height and weight
checked often
while taking Vyvanse. The doctor may stop treatment if a problem
is
found during these
check-ups.

This is not a complete summary of safety information for the use of
Vyvanse in the treatment of ADHD. For additional safety
information, please click here for Full Prescribing Information
[http://pi.shirecontent.com/PI/PDFs/Vyvanse_USA_ENG.pdf ]and
Medication Guide
[http://medguide.shirecontent.com/MEDGUIDE/PDFs/MG_Vyvanse_USA_ENG.pdf
], including Warning about Potential for Abuse, and discuss with
your doctor.

About Major Depressive Disorder (MDD) and Inadequate Response in
MDD

Major Depressive Disorder (MDD), also known as major depression,
is a mental disorder that causes depressed mood, loss of interest
or pleasure, feelings of guilt or low self-worth, disturbed sleep
or appetite, low energy, and poor concentration. MDD affects
approximately fourteen million patients in the United States alone,
and costs for treating this condition exceeded $83.1 billion in
2000. It is estimated that MDD will become the second leading cause
of morbidity worldwide across all ages by 2020.

While an extensive number of antidepressants have been approved
for monotherapy in MDD, many patients remain symptomatic by
incomplete resolution of MDD symptoms despite treatment with
antidepressant monotherapy at appropriate doses and trial duration.
These patients with an inadequate therapeutic response represent up
to two-thirds of patients treated with antidepressant monotherapy.
Commonly, these inadequate responders remain symptomatic with
respect to mood, concentration, motivation, and interest, often
reflected by impairment in multiple domains (eg, work/school,
social life, and home/family life). Major health authorities
recognize inadequate response in MDD as a valid target for
pharmacologic intervention, with two medications being currently
approved in the US and/or the EU.

Notes to editors

SHIRE PLC

Shire's strategic goal is to become the leading specialty
biopharmaceutical company that focuses on meeting the needs of the
specialist physician. Shire focuses its business on attention
deficit hyperactivity disorder, human genetic therapies,
gastrointestinal diseases and regenerative medicine as well as
opportunities in other therapeutic areas to the extent they arise
through acquisitions. Shire's in-licensing, merger and acquisition
efforts are focused on products in specialist markets with strong
intellectual property protection and global rights. Shire believes
that a carefully selected and balanced portfolio of products with
strategically aligned and relatively small-scale sales forces will
deliver strong results.

Statements included herein that are not historical facts are
forward-looking statements. Such forward-looking statements involve
a number of risks and uncertainties and are subject to change at
any time. In the event such risks or uncertainties materialize, the
Company's results could be materially adversely affected. The risks
and uncertainties include, but are not limited to, risks associated
with: the inherent uncertainty of research, development, approval,
reimbursement, manufacturing and commercialization of the Company's
Specialty Pharmaceuticals, Human Genetic Therapies and Regenerative
Medicine products, as well as the ability to secure new products
for commercialization and/or development; government regulation of
the Company's products; the Company's ability to manufacture its
products in sufficient quantities to meet demand; the impact of
competitive therapies on the Company's products; the Company's
ability to register, maintain and enforce patents and other
intellectual property rights relating to its products; the
Company's ability to obtain and maintain government and other
third-party reimbursement for its products; and other risks and
uncertainties detailed from time to time in the Company's filings
with the Securities and Exchange Commission.